The proliferation, differentiation and regulatory function of T cells in the intestinal lamina propria is thought to depend largely on their production of cytokines. Previously we have shown in nonhuman primates that intestinal lamina propria (LPL) T cells have high expression of IL-2 receptors, have high capacity for IL-2 production, and produce helper factors for immunoglobulin synthesis in response to intestinal pathogens. In the present study we investigated the response of nonhuman primate T cells to human recombinant IL-4 and have examined their capacity to produce B cell proliferation factors. T cells from MLN exhibited a dose-dependent proliferative response (3H-thymidine incorporation) when cultured with rIL-4. The response was dependent on the presence of phorbol myristate acetate (PMA) as a co-stimulus. In contrast, LPL T cells had a minimal response to rIL-4, but did not have responses to rIL- 2 and the mitogen concanavalin A. To investigate lymphokine production by T cells, culture supernatants from concanavalin A stimulated T cells were obtained. Using a Staph A Cowans (SAC) co- stimulation assay, it was shown that supernatants from both MLN and LPL T cells stimulate proliferation of MLN B cells. In addition, it was shown that mitogen activated LPL T cells produce substantially higher IFN-gamma bioactivity and have much higher levels of IFN-gamma mRNA than activated MLN T cells. These studies show for the first time that the two major lymphoid compartments of intestinal immune system, organized lymphoid cells in the mesenteric lymph nodes and diffusely scattered lymphocytes in the intestinal lamina propria, are fundamentally different in their production and utilization of the lymphokines IL-2, IL-4 and IFN- gamma.